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Syrian state television said that Defence Minister Daoud Rajha was killed in a blast in Damascus on Wednesday (July 18).
A suicide bomber who detonated explosives at a meeting of ministers and top security and military officials was a bodyguard who worked for the president's inner circle, a Syrian security source said.
Syria's state television reported that Assad's brother-in-law and top military official Assef Shawkat was also killed.
Security sources say that intelligence chief Hisham Bekhtyar was wounded and was undergoing surgery.
State television said Interior Minister Mohammad Ibrahim al-Shaar, who was reported killed in the blast by some Arab television stations, was in a "stable condition".
Two groups have claimed responsibility for the explosion.
Liwa al-Islam, an Islamist rebel group whose name means "The Brigade of Islam", said in a statement on its Facebook page that it "targeted the cell called the crisis control room in the capital of Damascus".
A spokesman for the group confirmed the claim by telephone.
The Free Syrian Army also claimed responsibility for the attack, according to spokesman Qassim Saadedine.

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